Warning to moms-to-be: Common medications could hamper fetal brain development
University of Nebraska Medical Center researchers Károly Mirnics (L) and Zeljka Korade say their newly published review of suspected connections between commonly prescribed drugs and childhood brain development points to “urgent pregnancy safety concerns.” Photo courtesy of the University of Nebraska Medical Center
A new, wide-ranging review of existing scientific data released Tuesday is pointing to the possibility that dozens of commonly prescribed drugs could adversely affect brain development in unborn children.
Evidence compiled by the scientific community so far suggests that unintended side effects of these drugs on the brain chemistry of children in utero presents “urgent pregnancy safety concerns,” especially for those who may be at particular genetic risk, the review shows.
The group of more than 30 drugs includes those whose side effects have been shown to inhibit the biosynthesis of brain cholesterol in animal studies. This process in unborn children is deemed essential for avoiding intellectual and developmental disabilities by promoting proper nerve cell connection formation and myelin production.
Antidepressants such as trazodone and fluoxetine and antipsychotic drugs such as cariprazine and aripiprazole are among those shown to affect brain cholesterol synthesis in mice.
The paper, published Monday in the scientific journal Brain Medicine, was authored by two University of Nebraska Medical Center academic researchers, Károly Mirnics and Zeljka Korade. Both have done previous work linking disruptions of sterol biosynthesis with common drugs, and they now have issued a new perspective on the available literature.
Their review found “concerning evidence” that brain development of unborn children could be at risk when exposed to these drugs. Additionally, up to 3% of the population that possesses a specific genetic variation could be particularly vulnerable to these medication effects, data shows.
The findings suggest medication safety protocols for pregnant women urgently need to be reviewed, Mirnics told UPI.
“I believe that new medications and existing medications should be scrutinized for their ability to disrupt cholesterol metabolism during development,” he said. “This could be done in animal models.” he said.
You’d want to make sure that if they do so, it would state clearly on the drug’s label, ‘Do not use during pregnancy.’ If that is the case, alternative medications should be used.”
The researchers said those who appear to be most at risk are mothers and children who have a genetic variant of the DHCR7 gene, which provides instructions for making an enzyme that plays a crucial role in the production of brain cholesterol, which is separate and distinct from the more familiar bloodstream cholesterol in other parts of the body.
“We know through animal studies and human fibroblast studies that if you have this genetic mutation in your genome, then you react to these cholesterol-inhibiting medications to a much greater degree,” Mirnics said, adding that if such drugs must be used during pregnancy, genetic testing of the mother and unborn child via amniocentesis to determine their risk would be appropriate.
The authors emphasized that patients should not discontinue prescribed medications without consulting their healthcare providers, while calling for more research to fully understand the implications of their findings.
The cause for concern is indeed “compelling,” agreed Andrew Brown, a biochemistry professor at the University of New South Wales in Sydney, who has similarly studied how commonly used antipsychotic drugs can interfere with brain sterol metabolism.
He told UPI in an email that when he looked at the Nebraska researchers’ previous findings, one of the questions he asked himself was, “Is there evidence that maternal exposure affects embryos?” He agreed the team presented “good data from mice studies to this effect.”
Brown said he believes it remains “a leap” to conclude that these drugs contribute to brain disorders in humans, “but given, ‘a,’ the complexity of brain development and, ‘b,’ the importance of cholesterol — and other sterols in it)– I wouldn’t be surprised if such a link emerges down the track,” he added.
Dr. Nenad Sestan a medical professor and brain development researcher at Yale University, told UPI the findings of the Nebraska review “are potentially very important.”
Sestan, who was not connected with the study, agreed that “medications that are perfectly safe for adults might not be so safe for the developing brain.
“The purpose of these studies are not to question the usefulness of the medication for adults, but to highlight that brain and body developments are dynamic and fragile processes, where a number of various environmental, lifestyle, genetic and treatment factors, especially in combination, can have profound influences on the heath of the unborn baby,” he said.
The studies in mice “are compelling, and we need further studies to understand these processes in humans,” he added.